{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T22:17:48Z","timestamp":1779142668208,"version":"3.51.4"},"reference-count":66,"publisher":"American Society for Clinical Investigation","issue":"24","license":[{"start":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T00:00:00Z","timestamp":1679356800000},"content-version":"vor","delay-in-days":89,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01 HL132251-02"],"award-info":[{"award-number":["R01 HL132251-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,22]]},"abstract":"<jats:p>\n                    Mutations in the\n                    <jats:italic>BRCA1<\/jats:italic>\n                    tumor suppressor gene, such as 5382insC (\n                    <jats:italic>BRCA1<\/jats:italic>\n                    <jats:sup>insC<\/jats:sup>\n                    ), give carriers an increased risk for breast, ovarian, prostate, and pancreatic cancers. We have previously reported that, in mice,\n                    <jats:italic>Brca1<\/jats:italic>\n                    deficiency in the hematopoietic system leads to pancytopenia and, as a result, early lethality. We explored the cellular consequences of\n                    <jats:italic>Brca1<\/jats:italic>\n                    -null and\n                    <jats:italic>BRCA1<\/jats:italic>\n                    <jats:sup>insC<\/jats:sup>\n                    alleles in combination with\n                    <jats:italic>Trp53<\/jats:italic>\n                    deficiency in the murine hematopoietic system. We found that\n                    <jats:italic>Brca1<\/jats:italic>\n                    and\n                    <jats:italic>Trp53<\/jats:italic>\n                    codeficiency led to a highly penetrant erythroproliferative disorder that is characterized by hepatosplenomegaly and by expanded megakaryocyte erythroid progenitor (MEP) and immature erythroid blast populations. The expanded erythroid progenitor populations in both BM and spleen had the capacity to transmit the disease into secondary mouse recipients, suggesting that\n                    <jats:italic>Brca1<\/jats:italic>\n                    and\n                    <jats:italic>Trp53<\/jats:italic>\n                    codeficiency provides a murine model of hematopoietic neoplasia. This\n                    <jats:italic>Brca1<\/jats:italic>\n                    \/\n                    <jats:italic>Trp53<\/jats:italic>\n                    model replicated Poly (ADP-ribose) polymerase (PARP) inhibitor olaparib sensitivity seen in existing\n                    <jats:italic>Brca1<\/jats:italic>\n                    \/\n                    <jats:italic>Trp53<\/jats:italic>\n                    breast cancer models and had the benefits of monitoring disease progression and drug responses via peripheral blood analyses without sacrificing experimental animals. In addition, this erythroid neoplasia developed much faster than murine breast cancer, allowing for increased efficiency of future preclinical studies.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.158257","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T12:01:09Z","timestamp":1667908869000},"source":"Crossref","is-referenced-by-count":1,"title":["BRCA1 and TP53 codeficiency causes a PARP inhibitor\u2013sensitive erythroproliferative neoplasm"],"prefix":"10.1172","volume":"7","author":[{"given":"Gerardo","family":"Lopez-Perez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3587-2250","authenticated-orcid":true,"given":"Ranjula","family":"Wijayatunge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly B.","family":"McCrum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sam R.","family":"Holmstrom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria E.","family":"Mgbemena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theodora S.","family":"Ross","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"232","published-online":{"date-parts":[[2022,12,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203334"},{"issue":"12","key":"B2","first-page":"4842","article-title":"Homology-directed dna repair, mitomycin-c resistance, and chromosome stability is restored with correction of a Brca1 mutation","volume":"61","author":"Moynahan","year":"2001","journal-title":"Cancer Res"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80202-6"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/35077232"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-11-0597"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nature03445"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806092105"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam7344"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(01)00269-6"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a016600"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biophys-051013-022737"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/ng1942"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2009.02.018"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01228-0"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-10-3011"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603392"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.12.075"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-018-05127-2"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-03-635599"},{"key":"B20","doi-asserted-by":"crossref","DOI":"10.1155\/2013\/928562","article-title":"A comprehensive focus on global spectrum of BRCA1 and BRCA2 mutations in breast cancer","volume":"2013","author":"Karami","year":"2013","journal-title":"Biomed Res Int"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/356215a0"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-05-506568"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90201-1"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-02-554634"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.478"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-06-719237"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1940710"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118828"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0158649"},{"key":"B30","unstructured":"Drew Scientific Inc. 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